Centrosome-centric view of asymmetric stem cell division

The centrosome is a unique organelle: the semi-conservative nature of its duplication generates an inherent asymmetry between ‘mother’ and ‘daughter’ centrosomes, which differ in their age. This asymmetry has captivated many cell biologists, but its meaning has remained enigmatic. In the last two decades, many stem cell types have been shown to display stereotypical inheritance of either the mother or daughter centrosome. These observations have led to speculation that the mother and daughter centrosomes bear distinct information, contributing to differential cell fates during asymmetric cell divisions. This review summarizes recent progress and discusses how centrosome asymmetry may promote asymmetric fates during stem cell divisions.

Download Full-text

On the edge: Evolution of polarity protein BASL and the capacity for stomatal lineage asymmetric divisions

10.1101/2021.08.05.455184 ◽

2021 ◽

Author(s):

Ido Nir ◽

Gabriel O Amador ◽

Yan Gong ◽

Nicole K Smoot ◽

Le Cai ◽

...

Keyword(s):

Cell Fate ◽

Cell Types ◽

Cell Fates ◽

Division Plane ◽

Asymmetric Cell Divisions ◽

Cell Divisions ◽

Distinct Cell ◽

Asymmetric Divisions ◽

Stem Cell Divisions ◽

Stomatal Lineage

Asymmetric and oriented stem cell divisions enable the continued production of patterned tissues. The molecules that guide these divisions include several polarity proteins that are localized to discrete plasma membrane domains, are differentially inherited during asymmetric divisions, and whose scaffolding activities can guide division plane orientation and subsequent cell fates. In the stomatal lineages on the surfaces of plant leaves, asymmetric and oriented divisions create distinct cell types in physiologically optimized patterns. The polarity protein BASL is a major regulator of stomatal lineage division and cell fate asymmetries in Arabidopsis, but its role in the stomatal lineages of other plants was unclear. Here, using phylogenetic and functional assays, we demonstrate that BASL is a dicot specific polarity protein. Among dicots, divergence in BASLs roles may reflect some intrinsic protein differences, but more likely reflects previously unappreciated differences in how asymmetric cell divisions are employed for pattern formation in different species. This multi-species analysis therefore provides insight into the evolution of a unique polarity regulator and into the developmental choices available to cells as they build and pattern tissues.

Download Full-text

Klp10A, a stem cell centrosome-enriched kinesin, balances asymmetries in Drosophila male germline stem cell division

eLife ◽

10.7554/elife.20977 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 14

Author(s):

Cuie Chen ◽

Mayu Inaba ◽

Zsolt G Venkei ◽

Yukiko M Yamashita

Keyword(s):

Stem Cell ◽

Cell Division ◽

Cell Fate ◽

Germline Stem Cell ◽

Germline Stem Cells ◽

Male Germline ◽

Mother And Daughter ◽

Stem Cell Divisions ◽

Stem Cell Division ◽

Male Germline Stem Cells

Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program. Concomitant with mother centrosome elongation, GSCs form asymmetric spindle, wherein the elongated mother centrosome organizes considerably larger half spindle than the other. This leads to asymmetric cell size, yielding a smaller differentiating daughter cell. We propose that klp10A functions to counteract undesirable asymmetries that may result as a by-product of achieving asymmetries essential for successful stem cell divisions.

Download Full-text

Emerging mechanisms of asymmetric stem cell division

The Journal of Cell Biology ◽

10.1083/jcb.201807037 ◽

2018 ◽

Vol 217 (11) ◽

pp. 3785-3795 ◽

Cited By ~ 42

Author(s):

Zsolt G. Venkei ◽

Yukiko M. Yamashita

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Division ◽

Asymmetric Cell Division ◽

Binary Outcomes ◽

Cellular Mechanisms ◽

Asymmetric Cell Divisions ◽

Cell Divisions ◽

Dividing Cells ◽

Stem Cell Division

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.

Download Full-text

Conservation and Divergence of YODA MAPKKK Function in Regulation of Grass Epidermal Patterning

10.1101/287433 ◽

2018 ◽

Author(s):

Emily Abrash ◽

M Ximena Anleu Gil ◽

Juliana L Matos ◽

Dominique C Bergmann

Keyword(s):

Cell Fate ◽

Cell Types ◽

Lineage Tracing ◽

Cell Fates ◽

Kinase Gene ◽

Asymmetric Cell Divisions ◽

Cell Divisions ◽

Asymmetric Divisions ◽

Species Specific ◽

Multicellular Organisms

AbstractAll multicellular organisms must properly pattern cell types to generate functional tissues and organs. The organized and predictable cell lineages of the Brachypodium leaf enabled us to characterize the role of the MAPK kinase kinase gene BdYODA1 in regulating asymmetric cell divisions. We find that YODA genes promote normal stomatal spacing patterns in both Arabidopsis and Brachypodium, despite species-specific differences in those patterns. Using lineage tracing and cell fate markers, we show that, unexpectedly, patterning defects in bdyoda1 mutants do not arise from faulty physical asymmetry in cell divisions but rather from improper enforcement of alternative cellular fates after division. These cross-species comparisons allow us to refine our interpretations of MAPK activities during plant asymmetric cell divisions.Summary StatementAnalysis of Brachypodium leaf epidermis development reveals that the MAPKKK, BdYODA1, regulates asymmetric divisions by enforcing resultant cell fates rather than driving initial physical asymmetries.

Download Full-text

Comment on "Variation in cancer risk among tissues can be explained by the number of stem cell divisions"

10.1101/024497 ◽

2015 ◽

Cited By ~ 1

Author(s):

Maxime Tarabichi ◽

Vincent Detours

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cell ◽

Cell Division ◽

Risk Groups ◽

Prevention Measures ◽

Cell Divisions ◽

Hepatocellular Carcinomas ◽

Major Subset ◽

Stem Cell Divisions ◽

Stem Cell Division

Tomasetti and Vogelstein (Science 347, 78–81, 2015) claimed that “primary prevention measures are not likely to be very effective” for many cancers because they arise mostly from random mutations fixed during stem cell division, independently of specific genetic or environmental factors. We demonstrate that their calculation for hepatocellular carcinomas overlooked a major subset of tumors proven to be preventable through vaccination. The problem, which is not limited to hepatocellular carcinoma, arises from the general reliance of their analysis on average USA incidences and the omission of incidences in specific risk groups.

Download Full-text

A hybrid model connecting regulatory interactions with stem cell divisions in the root

Quantitative Plant Biology ◽

10.1017/qpb.2021.1 ◽

2021 ◽

Vol 2 ◽

Author(s):

Lisa Van den Broeck ◽

Ryan J. Spurney ◽

Adam P. Fisher ◽

Michael Schwartz ◽

Natalie M. Clark ◽

...

Keyword(s):

Stem Cell ◽

Hybrid Model ◽

Regulatory Networks ◽

Quiescent Center ◽

Specific Expression ◽

Agent Based ◽

Cell Divisions ◽

Cell Type Specific Expression ◽

Stem Cell Divisions ◽

Cell Niche

Abstract Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.

Download Full-text

Histone Acetyltransferases and Stem Cell Identity

Cancers ◽

10.3390/cancers13102407 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2407

Author(s):

Ruicen He ◽

Arthur Dantas ◽

Karl Riabowol

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Epigenetic Modification ◽

Cell Types ◽

Histone Acetyltransferases ◽

Specific Cell ◽

Cell Fates ◽

Cell Identity ◽

Hematopoietic Stem

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.

Download Full-text

The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans

Development ◽

10.1242/dev.124.15.2875 ◽

1997 ◽

Vol 124 (15) ◽

pp. 2875-2888 ◽

Cited By ~ 5

Author(s):

L.A. Wrischnik ◽

C.J. Kenyon

Keyword(s):

Stem Cell ◽

Regulatory Gene ◽

Epidermal Cells ◽

Body Axis ◽

Wild Type ◽

Hox Gene ◽

C Elegans ◽

Cell Divisions ◽

Body Regions ◽

Stem Cell Divisions

In C. elegans, six lateral epidermal stem cells, the seam cells V1-V6, are located in a row along the anterior-posterior (A/P) body axis. Anterior seam cells (V1-V4) undergo a fairly simple sequence of stem cell divisions and generate only epidermal cells. Posterior seam cells (V5 and V6) undergo a more complicated sequence of cell divisions that include additional rounds of stem cell proliferation and the production of neural as well as epidermal cells. In the wild type, activity of the gene lin-22 allows V1-V4 to generate their normal epidermal lineages rather than V5-like lineages. lin-22 activity is also required to prevent additional neurons from being produced by one branch of the V5 lineage. We find that the lin-22 gene exhibits homology to the Drosophila gene hairy, and that lin-22 activity represses neural development within the V5 lineage by blocking expression of the posterior-specific Hox gene mab-5 in specific cells. In addition, in order to prevent anterior V cells from generating V5-like lineages, wild-type lin-22 gene activity must inhibit (directly or indirectly) at least five downstream regulatory gene activities. In anterior body regions, lin-22(+) inhibits expression of the Hox gene mab-5. It also inhibits the activity of the achaete-scute homolog lin-32 and an unidentified gene that we postulate regulates stem cell division. Each of these three genes is required for the expression of a different piece of the ectopic V5-like lineages generated in lin-22 mutants. In addition, lin-22 activity prevents two other Hox genes, lin-39 and egl-5, from acquiring new activities within their normal domains of function along the A/P body axis. Some, but not all, of the patterning activities of lin-22 in C. elegans resemble those of hairy in Drosophila.

Download Full-text